Unsaturated nitriles containing carbonyl groups and preparation thereof



United States Patent D Int. Cl. C07c 121/3 0, 121/48, 121/70 US. Cl.260-464 14 Claims ABSTRACT OF THE DISCLOSURE Process of preparingunsaturated carbonyl group containing nitriles of the formula:

wherein R and R are each hydrogen, alkyl, cycloalkyl or aryl and can beconjoined to form a ring by reacting u,- dimethyl-y-cyanobutyraldehydewith an aldehyde or ketone containing methyl or methylene groups in thepresence of a basic condensing agent. The nitriles thus produced areuseful compounds and can, for example, be employed as a stabilizer fornitric ester.

This invention relates to unsaturated nitriles containing carbonylgroups. More particularly, it relates to the preparation of unsaturatednitriles containing carbonyl groups by the condensation ofot-dimethylcyanobutyraldehyde and an aldehyde or ketone containingmethyl or methylene groups in the presence of a basic condensationagent.

The following are illustrative of the aldehydes and ketones which aresuitable for condensation with DCBA, in accordance with the invention:aliphatic aldehydes such as acetaldehyde, propionaldehyde, butyraldehydeand the like, and ketones such as acetone, methyl ethyl ketone, methylisopropyl ketone, methyl isobutyl ketone and the like, cycloaliphaticketones such as cyclobutanone, cyclopentanone, cyclohexanone, uandfl-tetralones, etc., and aromatic ketones such as acetophenone,p-bromphenyl ethyl ketone, phenyl benzyl ketone, dibenzyl ketone,desoxybenzoin and the like. The latter may contain as substituents ontheir nuclei, moieties not affected or reactive under the reactionconditions.

In accordance with the invention, it has now been found thatunsaturated, carbonyl group-containing nitriles of the formula:

wherein R and R are each a hydrogen atom, alkyl, cycloalkyl or aryl, orR and R can be conjoined to form a ring and can be prepared by thecondensation of egocdirnethyl-v-cyanobutyraldehyde and an aldehyde orketone containing methyl or methylene groups, in the presence of basiccondensing agents.

It is known (Houben-Weyl, vol. 7, part 1, pp. 79-80) (1954) thataldehydes which have a branching at the otcarbon atom enter intocondensation reactions with other aldehydes (e.g., aldol condensationfollowed by dehydration) much less readily than those aldehydes whichhave no branching at the at position. It is obvious to the skilledtechnical man that the reactivity of an aldehyde is even 'ice less whengreater branching is present, as in the case, for example, of analdehyde having an aldehyde group linked to a tertiary carbon atom. Whenketones are used instead of aldehydes as reactants for reaction withaldehydes that are branched at the a-position, a further retardation ofthe reaction is to be expected. Accordingly, heretofore, unsaturatedcondensation products of 0c,- dirnethyl-y-cyanobutyraldehyde (DCBA) havebeen prepared only by utilizing as reactants compounds having highlyreactive methylene groups, such as malonic acid or acetoacetic acid. Itwas not, accordingly, to have been expected that the condensation ofa,u-dimethyl-'y-cyano butyraldehyde with carbonyl compounds which do nothave especially activated methyl or methylene groups would take placeeasily. This was all the more true because of the fact that themethylene group adjacent the nitrile group might enter the reaction, sothat a selfcondensation of the DCBA would have to be anticipated whichwould reduce the yield. In case of the use of alkaline condensingagents, a conversion of the DCBA to 5,S-dimethyl-6-oxypiperidone-(2) wasalso to be expected. Furthermore, in the presence of alkaline condensingagents, there would be no Way of preventing the condensation productsthat might be formed with aldehydes and ketones from being convertedinto piperidone derivatives the same as the cbndensation product formedwith malonic acid.

It is therefore, surprising that conditions have been found under whicha,a-dimethyl-'y-cyanobutyraldehyde can be condensed with an aldehydeorketone to form the unsaturated carbonyl group-containing nitriles ingood yield, the many possible side reactions being suppressed.

In order to successfully carry out the condensation, it was necessary toprovide conditions which would exclude insofar as possible anysaponificatio n of the nitrile groups. It was established that the useof basic condensing agents under carefully controlled temperatureconditions was necessary to this end.

The following are instances of basic condensing agents which have provedsuitable for use herein: hydroxides, carbonates, alcoholates, hydridesand amides of the alkali metals, and preferably of sodium or potassium;the hydroxides and alcoholates of the alkaline earth metals such asbarium; tertiary amines such as triethylamine; quaternary ammoniumcompounds such as benzyl trimethyl ammonium hydroxide, as well as knowntypes of basic ion exchangers such as Lewatit M-600 and MP- 500, Dowex land Dowex 21K, Duolit A7+A30 and Duolit 101 D, and Permutit ESB. Thereaction temperature is preferably maintained between -20 C. and 100 C.,a lower condensation temperature being applied when strongly basiccondensing agents are involved than in the case of more weakly basiccondensing agents. For example, when using potassium hydroxide or sodiumalcoholate, it has proven advantageous to operate at temperatures from-l0 C. to 40 C. When barium hydroxide is used as the condensing agent,temperatures be tween 10 and C. have proven most advantageous, and inthe case of basic ion exchangers, the preferred temperatures are between50 and C.

The quantity of basic condensing agent to be used, other than in thecase of the basic ion exchanger, is between 0.03 and 5 mole-percent, andpreferably between 0.08 and 3 mole-percent with reference to the DCBA.The amount of basic ion exchanger can vary widely, according to whetherthe ion exchanger is added to the mixture of reactants or whether themixture of reactants is continuously fed through a reactor filled withinion exchanger. The basic exchanger remains active for a long time and,if desired, can be regenerated according to the conventional methods.

4,4-dimethyl-6-cyanohexene-(2)-al-(1),

2,4,4-trimethyl-6-cyanohexene- (2 -al- 1 4, 4-dimethyl-Z-phenyl-6-cyanohexene- 2 -al- 1 ,5 -dimethyl-7-cyanoheptene- 3-one- (2 3,5 ,5 -trimethyl-7 -cyanoheptene- 3 )-one- (2)2,6,6-trimethyl-8=cyanoctene- (4) -one 3 phenyl- (3,3-dimethyl-5-cyanopentene- 1 -y1) kentone,

and

2- (2, 2-dimethyl-4- cyanobutylidene) cyclohexanone.

The compounds manufactured according to the invention can be used asstabilizers, e.g., for nitric ester.

The yields in the case of the above-named condensation products areusually greater than 60% with reference to the amount of reacted DCBA.

of 95 to 98C. The 2,4-dinitrophenylhydrazone was precipitated by theaddition of the alcoholic solution of the dimethylcyanoheptenone of asolution of 2,4-dinitrophenylhydrazine in phosphoric acid and ethylalcohol. M.P. 144 C. (after recrystallization from ethanol).

EXAMPLE 5 1250 g. of DCBA was heated to 40 C. with 870 g. of acetone ina flask equipped with an agitator, a reflux condenser and a droppingfunnel. At this temperature, a dispersion of 30 g. of Ba(OH) in 110 g.of Water was added with strong agitation in such a manner that thetemperature did not exceed 40 C. After a total of 25 hours at 40 C., themixture was cooled. The barium hydroxide was then precipitated by theintroduction of carbonic acid as a carbonate, filtered and washed withacetone. Acetone and water were removed from the filtrate bydistillation at normal pressure and small amounts of DCBA along withresidual water were removed by distillation at 40 C. and 0.5 torr.

From the residue amounting to 1360 g., a distillable fraction of 823 g.was separated by means of a rotating evaporator at 195 C. and 0.5 mm.[Hg]. The separated Condensation Moles Percent Yield as Mole-percent ofcondensing agent of Temp. Time of DCBA percent of Moles of aldehyde orketone (with ref. to DCBA) solvent 0.) (H12) reacted reacted DCBA 13.5of acetone. 5. 5 48 I 55. 9 10 of acetone 8 63 61. 1 1 of acetone... 6.6NazCOa 74-82 8 24 59. 2 -do 0.6 of benzyl dimethyl ammonium 40 5 44 54.2

hydroxide. 15 of acetone 1.75 Ba(OH)2 5.55 120..-. 40 76 42. 0 1 ofacetone 0.42 NaOCHa, 6 91 40. 5 -tl0. 0.1 KOH 25 5 78 60. 5 1 0.--. 0.05potassium ter butylat 30 6 88 59. 1 10 of acetone Lewatit M600 77-83 470 b 58. 0 10 of methyl ethyl ketone 0. 9 KOH 30 2. 5 79 v 52. 0 1.1 ofmethyl isopropyl ketone... 0.3 KOH- 20 8 80 d 60. 5 1 of methyl isobutylketone 3.5 KOH 7 66. 5 e 56. 8 1 of 3.5 KOEL- 40 6 60 f 70. 0 1 of 2 NaH-5 2. 6 8 33. 0 1 of 2.5 NaNHz.-. 10 5 44 36. 1 3.2 of acetaldehyde 0.66KO 30 6 16 65 B 5,5-dimethyl-7-cyanoheptene-(3)-one-(2). B.P.1o: 95960.; CroHrsNO (moLwt. 165). Calcd (percent): 0 72 7; H, 9.1; N, 8.5.Found (percent): C, 72.46; H, 9.22; N, 8.46. 2,4-dinitrophenylhydrazoneM.P. 144 C. (recrystallized from ethanol): Calcd (percent): N, 20.25;Found (percent): N, 20.30.

b 9.5% of the reacted DCBA was isolated in the form of 5,5-d1methyl-6acetonylpiperidone-(2) (M.P. 105 C. recrystallized from cyclohexan'e).OmI-11vN02 (mol. wt. 183). Calcd (percent): 0, 65.5; H, 9.30; N, 7.65.Found (percent): 0, 65.75; H, 9.45; N, 9.29.

n 3,5,5-trimethyl-7-cyanoheptene(3)-one-(2). B.P.o.52109 0.; CnHnNO(mol. wt. 179). Calcd (percent): 0, 73.7; H, 9.50; N, 7.83. Found(percent): O, 74.09; H, 9.90; N, 7.57.

The condensation and purification processes used in Examples 1, 5, 9 and16 are described hereinafter by way of exemplification.

EXAMPLE 1 1250 g. of a,a-dimethyl-' -cyanobutyraldehyde (DCBA) was mixedwith 780 g. of acetone in a sulfation flask provided with an agitatorwhich was kept running at a good speed. 15 g. of 30% aqueous solution ofKOH was slowly dripped into the flask with cooling. The dripping in ofthe KOH was so controlled that, under continuous external cooling byrunning water, the reaction temperature did not exceed 20 C. After ashort reaction time (30 min.) the mixture assumed a yellowish color.After 5% hours the mixture was acidified with HCl (diluted 1:1) to a pHof 5, the salt was washed out with water, and the remaining organicphase fractionated in vacuo. The first runnings, consisting of residuesof acetone, water and some DCBA, were drawn off with a water-jet vacuumpump, and the remainder distilled at 4 torr. Between 43 and 95 C., mostof the unreacted DCBA (633 g.) passed over and, after a smallintermediate fraction amounting to 38 g. had distilled over at 95 to 125C., the crude 5,5-dimethyl-7-cyanoheptene-(3)-(2) remaining boiled at120 to 180 C. By fractionation through a column, 440 g. of dirnethylcyanoheptenone was obtained, having a BP2,6,6-trirnethyl-8-cyanoctene-(4)-one-(3). B.P-o,2; 142 0.; C N NO (mol.t. 193). Calcd (percent): 0, 74.6; H, 9.84; N, 7.25. Found (percent): 0,74.28; H, 10.2; N, 7.87.

e 2,7,7-trlmethyI-Q-cyanononene-(5)-one-(4) or 3-isopropyl-5,5-dlmethyl-7cyanoheptene-(3)-one-(2). B.P.u.z: l56158 0.; ClIiHElNO (mol. wt. 207).Calcd (percent): 0, 75.36; H, 10.15; N, 6.76. Found (percent): 0, 75.23;H, 10.17; N, 6.69.

Phenyl-(3,3-dimethyl-5 cyanopentene-(l)-y1)ketone. B.P.o.4: 174- 178 0.;C15H11NO (mol. Wt. 227). Calcd (percent): 0, 79.2; H, 7.50; N, 6.16.Found (percent): 0, 79.14; H, 7.66; N, 6.73.

g 4,4-dimethyl-6-cyanohexene-(2)-al-(1). B.P.12: 163166 0.; CeHraNO(mol. wt. 115). Calcd (percent): N, 9.28. Found (percent): N, 9.42.

fraction consisted of 300 g. (2.4 moles) of unreacted DCBA and 523 g. of5,5-dimethyl-7-cyanoheptene-3-(2).

EXAMPLE 9 400 ml. of Lewatit M-600 ion exchanger (freshly activated with10% NaOH and washed with water), 1250 g. of DCBA and 580 g. of acetonewere heated in a flask having a reflux condenser and an agitator.Refluxing began at a sump temperature of 77 C. A sump temperature of 83C. was reached after 4 hours and then the mixture was cooled down andfiltered off from the ion exchanger. Thereafter the lowest-boilingfractions were removed by distillation with a water-jet vacuum pump to asump temperature of 90 C. Fractionation was then carried out at 3 torr,300 g. of unreacted DCBA (2.4 moles) were obtained between 60 and 90 C.,and between 90 and C., 632 g. of crude 5,5-dimethyl-7-cyanoheptene-(3)-one-(2) were recovered. From the latter, 610 g. of puresubstance were obtained having a HP, of 94 to 98 C. Above 150 C., 110 g.of a viscous substance distilled out (most of it at C. and 1 torr),which hardened in a crystallized manner in the receiver, and whichfollowing recrystallization from cyclohexane, melted at 105 C. Theinfra-red spectrum indicated the presence of piperidone.

EXAMPLE 16 375 g. of DCBA was mixed at C. with 2.24 g. of 50% KOH in aflask provided with a dropping funnel, an agitator and a refluxcondenser, and which had been installed in a cooling bath and then 140.8g. of freshly distilled acetaldehyde was dripped in over a period of 4hours in such a manner that the reaction temperature of 30 C. was notexceeded. After an additional 2 hours at 30 C., the mixture wasacidified slightly (pH 5) with dilute hydrochloric acid. After theaddition of 30 ml. of H 0 and 50 ml. of benzene, the organic phase wasseparated oif. The aqueous phase was extracted three more times byshaking with 50 ml. of benzene each time, and the combined benzenesolutions were fractionated through a short column.

Following removal of unreacted acetaldehyde, adherent water and benzeneunder normal pressure, 315 g. of DCBA were recovered at BP 115 to 125 C.(corresponding to a conversion of 16%). Following a brief first-runningsperiod, 47.1 grams passed over at a BP of 163 to 166 C. (yield 65% ofthe theory with reference to reacted cyanobutyraldehyde).

The types of known basic ion exchange resins listed in col. 2, are ofthe following chemical nature:

Lewatit M-600 is a very strong basic ion exchange resin on the basis ofpolystyrene.

Lewatit MP-SOO is an extremely strong basic ion exchange resin on thebasis of polystyrene as well.

Dowex 1 is a polymerisate of styrene with divinyl benzene bearingtrimethyl benzyl ammonium groups.

Dowex 21K has the same chemical nature.

Duolit A7 is a phenolic resin with secondary amine groups.

Duolit A30 is an epoxy polyamine resin with tertiary and quaternaryamine groups.

Duolit 101 D is a polystyrene resin with tertiary amine groups.

Permutit ESB is a cross-linked polystyrene resin with quaternaryammonium groups.

We claim:

1. An unsaturated carbonyl group containing nitrile of the formula:

wherein R and R are each a member selected from the group consisting ofhydrogen, alkyl containing 1 to 4 carbon atoms, phenyl, and benzyl andwherein R and R together can be cojoined to form a cyclobutyl,cyclopentyl or cyclohexyl ring.

2. An unsaturated carbonyl group containing nitrile according to claim 1designated 4,4-dimethyl-6-cyanohexene- (2)-a1-( 1 3. An unsaturatedcarbonyl group containing nitrile according to claim 1 designated2,4,4-trimethyl-6-cyanohexene-(2) -al-(1).

4. An unsaturated carbonyl group containing nitrile according to claim 1designated 4,4-dimethyl-2-phenyl-6- cyanohexene-(Z -all 5. Anunsaturated carbonyl group containing nitrile according to claim 1designated 5,5-dimethyl-7-cyanoheptene-(3 )-one-(2) 6. An unsaturatedcarbonyl group containing nitrile according to claim 1 designated3,'-5,5-trimethyl-7cyanoheptene-(S )-one- (2) 7-. An unsaturatedcarbonyl group containing nitrile according to claim 1 designated2,6,6-trimethyl-8-cyanoctene-(4) -one-(3 8. An unsaturated carbonylgroup containing nitrile according to claim 1 designatedphenyl-(3,3-dimethyl-5- cyanopentene-( 1 -yl) -ketone.

9. An unsaturated carbonyl group containing nitrile according to claim 1designated 2-(2,2-dimethyl-4-cyanobutylidene)-cyclohexanone.

10. Process for the preparation of an unsaturated carbonyl groupcontaining nitrile of the formula:

wherein R and R are each a member selected from the group consisting ofhydrogen, alkyl containing 1 to 4 carbon atoms phenyl and benzyl andwherein -R and R together can be cojoined to for ma cyclobutyl,cyclopentyl or cyclohexyl ring which comprises reacting at a temperatureof from 10 to C. u,a-dimethyl-'y-cyano butyraldehyde with a memberselected from the group consisting of aldehydes and ketones containing amethyl or methylene group and the requisite substituents to yield theabove defined R and R in the presence of 0.03 to 5 mol-percent referredto said a,a-dimethyl-v-cyanobutyraldehyde of a basic condensing agentand recovering said nitrile in a yield greater than 60 percent based onthe amount of said a,a-dimethyl-y-cyanobutyraldehyde reacted.

11. Process according to claim 10 wherein said basic condensing agent isa member selected from the group consisting of alkali metal hydroxides,carbonates, alcoholates, hydrides and amides, alkaline earth metalhydroxides and alcoholates, tertiary amines and quaternary ammoniumhydroxides.

12. Process according to claim 10 wherein said basic condensing agent isused in an amount of 0.08 to 3-molepercent referred to saida,et-dimethyl-'y-cyanobutyraldehyde.

13. Process according to claim 10 wherein as basic condensing agent a'basic ion exchanger is employed.

14. Process according to claim 10 wherein said reaction is effected inthe presence of an inert solvent.

References Cited UNITED STATES PATENTS 2,564,131 8/1951 Schreyer260-4659 X 2,969,359 l/l961 De Benneville 260-593 X 3,060,236 10/1962Kollar et al. 260465.9 X

FOREIGN PATENTS 779,910 3/1968 Canada.

CHARLES B. PARKER, Primary Examiner D. H. TORRENCE, Assistant ExaminerUS. Cl. X.R. 260-294], 465, 465.9, 466, 566

